Low doses of fenofibrate and bezafibrate stimulate renal 2-oxoglutarate dehydrogenase (2-OGDH) in protein-restricted rats

Abstract

2-oxoglutarate dehydrogenase (2-OGDH) is the key regulatory enzyme of cell metabolism. It has been previously demonstrated that in rats subjected to protein restriction low, clinically relevant doses of fibrates up-regulate liver 2-OGDH and promote 2-oxoglutarate catabolism. The aim of the present study was to evaluate the effect of low doses of fenofibrate and bezafibrate on renal 2-OGDH complex in rats fed low-protein chow. Fibrates were administered for 14 days to Wistar male rats at one daily dose of 5, 10 or 20 mg/kg b.wt./day. The 2-OGDH activity was assayed spectrophotometrically. The mRNA levels for 2-OGDH catalytic subunits (E1 and E2) and PPARα were quantified by means of semi-quantitative reverse-transcription-PCR. 2-OGDH activity increased in response to administration of fenofibrate and bezafibrate (by 11, 24, 32% and 9, 12, 21%, respectively). The difference was statistically significant for the doses of 10 and 20 mg/kg b.wt of fenofibrate (p < 0.001) and the highest dose of bezafibrate (p < 0.05). The stimulation of 2-OGDH was not accompanied by changes in mRNA levels for E1 and E2. In addition, the mRNA level for PPARα did not change. It is conceivable that fibrate-induced stimulation of 2-OGDH activity can affect renal metabolism and contribute to changes in kidney functions.